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Utilization of N-fluoroalkyl-1,2,3-triazoles in organic synthesis
Markos, Athanasios ; Beier, Petr (advisor) ; Veselý, Jan (referee) ; Hanusek, Jiří (referee)
Athanasios Markos Abstract This Thesis deals with denitrogenative transformations of N-fluoroalkyl-1,2,3-triazoles, easily available heterocycles via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of safe and stable N-fluoroalkyl azides and alkynes. The introductory chapter describes general approaches towards N1-substituted 1,2,3- triazoles, methods of N1-,-difluoroalkyl-1,2,3-triazoles preparation and both, transition metal-catalyzed and transition metal-free transformations of N1-substituted 1,2,3- triazoles. In the first part of the Thesis, rhodium-catalyzed reactions of N-fluoroalkyl-1,2,3-triazoles are described. Rhodium-catalyzed reactions of N-fluoroalkyl-1,2,3-triazoles in presence of suitable reagents provide access to five-membered N-fluoroalkyl heterocycles, 2- fluoroalkyl oxazoles and ketamides. In the second part of the Thesis, both Brønsted and Lewis acid-mediated transformations of N-fluoroalkyl-1,2,3-triazoles leading to stereodefined N-alkenyl compounds, such as enamides, enimines, amidines and other are discussed. The robustness of the method is showcased on gram scale syntheses and preparation of a drug analogue. At last, thermally-induced rearrangement of N-fluoroalkyl-1,2,3-triazoles to 3-fluoroalkyl-2H- azirines and the proposed mechanism of the reaction are described.
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Mechanisms of metal-catalyzed reactions: an electrospray ionization mass spectrometry approach
Anania, Mariarosa ; Roithová, Jana (advisor) ; Hanusek, Jiří (referee) ; Slanina, Tomáš (referee)
Mass spectrometry, ion spectroscopy, NMR and quantum-chemical calculations are commonly combined to study the structures, properties and reactivity of intermediates in metal- catalyzed reactions. However, our ability to identify the main species present in solution by electrospray ionization mass spectrometry (ESI-MS) and to confirm whether these species are indeed reactive intermediates involved in the study reactions remains limited. Thus, we developed a new method combining isotope labeling with kinetic data extraction for the identification and analysis of intermediates in reaction mixtures termed delayed reactant labeling (DRL). Accordingly, this thesis is divided into 5 Chapters. Chapter 1 gives an overview of ESI-MS as a tool for studying the mechanisms of metal-catalyzed reactions, focusing on gold chemistry. Chapter 2 describes the experimental (ESI-MS, ion spectroscopy and gas chromatography) and theoretical (DFT) methods used in this thesis and the corresponding instrumentation. Chapter 3 details the development of the delayed reactant labeling (DRL) as a technique for studying reaction kinetics by mass spectrometry and examples how it was used to investigate problems in the following chapter. Chapter 4, shows that a Au(I) complex can act as a strong base in a solution containing water...
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Synthesis and Design of Potentially Antibacterial Active Compounds
Kozic, Ján ; Vinšová, Jarmila (advisor) ; Doležal, Martin (referee) ; Hanusek, Jiří (referee)
University: Charles University in Prague Faculty: Faculty of Pharmacy in Hradec Králové Department: Department of Inorganic and Organic Chemistry Candidate: Ing. et Mgr. Ján Kozic Supervisor: Prof. RNDr. Jarmila Vinšová, CSc. Title of Doctoral Thesis: Synthesis and Design of Potentially Antibacterial Active Compounds This work deals with the synthesis of benzanilides and their analogues as the potentially antimycobacterial active compounds. In the theoretical part of the work there is a description of tuberculosis (TBC) as a mycobacterial infectious disease and a short characteristic of recent antituberculotic drugs. The most important features of both, which determine the imperfection of recent antitubeculotics and the long-term multidrug TBC treatment, are emphasised. Further, some of the potential targets, useful for the development of new and more effective antituberculotics, are reviewed. Finally, there is a short overview of biological properties of benzanilides and thiobenzanilides and a more in depth characteristic of stereochemical properties of these compounds. In the experimental part of the work there are presented 100 benzanilide derivatives and their analogues. Ninety-two of these compounds are original, which have not been described in literature yet. For all of the compounds there...
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